Objective      To determine the effect of hepatitis C core protein on methylation modification of secreted frizzled-related protein (SFRP) genes.       Methods      Hepatoma cell line SMMC-7721 was infected with AdCore to develop an

in vitro

over-expression model. At 36 h after infection

the mRNA expression level of SFRP genes were detected with reverse transcriptase PCR in core-expressing SMMC-7721 cells. Cells were further demethylated with 5-aza-2′-deoxycytidine (DAC) for 96 h

and then infected with AdCore or AdGFP for 36

h. Methylation modification of CpG islands within SFRPs promoter region were assayed by methylation specific PCR (MSP) and bisulfite sequencing analysis. In addition

the expression level of methyltransferase Dnmt1 and Dnmt3a were detected by Western blotting.       Results      mRNA expression level of SFRP2 and SFRP5 gene were sharply reduced in core-expressing SMMC-7721 cells. Methylation analysis indicated that HCV core protein induced hypermethylation of CpG islands within SFRP5 promoter regions. Moreover

this modification was partially mediated by DNA methyltransferase Dnmt1 and Dnmt3a.       Conclusion      HCV core protein can induce hypermethylation in SFRP5 gene

which plays an important role in the pathogenesis of hepatocellular carcinoma.